1. Field of the Invention
The present invention relates to a disinfecting solution for a nonionic soft contact lens, and particularly relates to a disinfecting solution for a nonionic soft contact lens which solution contains at least polylysine as a disinfectant.
2. Description of Related Art
A disinfecting solution for a soft contact lens has been prepared by using polyhexamethylene biguanide (PHMB) and polyquaterniums as disinfectants for the soft contact lens. PHMB has a biguanide group as a repeating unit of its main chain, and the polyquaterniums have a quaternary ammonium group as a repeating unit of their main chains. The biguanide group and the quaternary ammonium group have positive charges in an aqueous solution, so that PHMB and the polyquaterniums electrostatically adsorb to negatively charged phospholipids existing in cell membranes of microorganisms, thereby exhibiting disinfecting effects. Although the disinfecting effects of PHMB and the polyquaterniums are powerful, these disinfectants exhibit high degrees of cytotoxicity, so that the use of PHMB and the polyquaterniums at an extremely high concentration should be avoided. On the other hand, even where those disinfectants are used at a relatively low concentration, the disinfectants tend to accumulate on a surface of the contact lens subjected to a hydrophilic treatment, which surface is negatively charged, giving rise to a problem of toxicity of the accumulated disinfectants. Under the above-described circumstances, efforts have been made to develop a disinfectant which exhibits a high degree of disinfecting effect and a low degree of cumulative toxicity with respect to the soft contact lens. Also, studies have been made to provide a disinfectant configured to reduce the cumulative toxicity with respect to the soft contact lens. However, such disinfectants have not been obtained yet.
On the other hand, polylysine used for disinfecting the contact lens is known as a polymer disinfectant, like the above-described PHMB and polyquaterniums. Polylysine has a lysine which is an amino acid, as a repeating unit, and considered to exhibit the disinfecting effect by electrostatic adsorption to surfaces of the microorganisms via a primary amine group. Further, polylysine has an extremely low degree of toxicity, since it has the lysine which is the amino acid, as the repeating unit. The extremely low degree of toxicity of polylysine is proved by a cytotoxicity test in which the IC50 value of polylysine is confirmed to be about several hundredth part of that of PHMB, for example. Accordingly, in the case where polylysine is used, a risk of eye disorders is evidently lower than in the case where PHMB is used, assuming that substantially the same amount of polylysine and PHMB accumulate on the contact lens.
However, it was revealed that where a component having a high degree of ionic strength is contained in the aqueous solution together with polylysine, the electrostatic adsorption of polylysine to the surfaces of the microorganisms is hindered, resulting in deterioration of the disinfecting effect, since the primary amine group of polylysine, which group is the active site of disinfection, has a weaker positive charge in the aqueous solution, than the biguanide group of PHMB and the quaternary ammonium group of the polyquaterniums.
Moreover, the electrostatic adsorption of the disinfectant is hindered by additives such as a surfactant, a buffer, a tonicity agent and a chelating agent, which are generally contained in the disinfecting solution for the soft contact lens, together with a disinfecting component (the disinfectant). Particularly, the tonicity agent is contained at a high concentration in the disinfecting solution for the soft contact lens, so that where an inorganic tonicity agent such as NaCl having a high degree of ionic strength (electric conductivity) exists in the disinfecting solution, together with polylysine, the disinfecting effect of polylysine is considerably deteriorated. Thus, where polylysine is used as the disinfectant, problems may be caused by the additives which do not cause problems when they are used together with the conventionally used disinfectants such as PHMB and the polyquaterniums.
For the reasons described above, in order for the disinfecting solution using polylysine having the low degree of toxicity to exhibit a sufficiently high disinfecting effect, precise reconsideration of the composition of the disinfecting solution is required.
By the way, JP-A-2000-84052 proposes to use, as the disinfecting solution, a contact lens solution containing the amino acid and/or a nonionic tonicity agent together with ε-polylysine used as a sterilizing component. This publication discloses examples of the contact lens solution containing components which increase the ionic strength, such as sodium phosphate, sodium glutamate and sodium chloride, and examples of the contact lens solution in which the nonionic tonicity agent such as propylene glycol is used in combination with a boric acid. JP-A-2006-201247 proposes a contact lens disinfecting and preserving solution containing an organic cationic compound and a lactic acid together with ε-polylysine, and a contact lens disinfecting and preserving solution further containing inositol or glycerol together with the organic cationic compound, the lactic acid and ε-polylysine. This publication discloses examples of the contact lens disinfecting and preserving solution containing the boric acid used as a pH buffer together with the above-indicated components.
However, in the case where an osmotic pressure of the disinfecting solution is adjusted by using the nonionic tonicity agent in the form of a low-molecular-weight polyhydric alcohol, a neutral amino acid and the like, which are disclosed in the above-indicated publications, swelling of a nonionic soft contact lens is likely to be caused by the nonionic tonicity agent. Accordingly, where tonicity is adjusted by increasing the osmotic pressure of the disinfecting solution to about 290 mOsm/kg by using the nonionic tonicity agent only, the nonionic soft contact lens considerably swells such that its dimensions exceed prescribed limits. On the other hand, in the case where auxiliary disinfecting components having an antiseptic effect, such as the boric acid and the lactic acid, are used together with polylysine, for the purpose of supplementing the disinfecting effect of polylysine to improve the disinfecting effect of the disinfecting solution, the use of the boric acid gives rise to problems of an increase of cytotoxicity of the disinfecting solution and a dimensional change of the nonionic soft contact lens, while the use of the lactic acid gives rise to an inherent problem that the lactic acid in the form of crystals is deposited on the surface of the nonionic soft contact lens, as pointed out in Japanese Patent No. 3894945.
On the other hand, in order to further improve the disinfecting effect of the disinfecting solution, proposals have been made regarding use of a second disinfectant in combination with polylysine used as a first disinfectant. For example, Japanese Patent No. 4255839 proposes a contact lens solution containing polylysine, a polyphosphoric acid (salt) and a nitrogen-containing organic antimicrobial agent (such as PHMB and the polyquaterniums). However, the use of the polyphosphoric acid (salt) is effective to prevent polylysine from adsorbing to the contact lens, but gives rise to a problem of deterioration of the disinfecting effect of polylysine. Further, the nitrogen-containing organic antimicrobial agents such as PHMB and the polyquaterniums, which have more powerful disinfecting effects than polylysine, cannot be effectively prevented from adsorbing to the contact lens, so that the disinfecting solution cannot sufficiently exhibit the disinfecting effect, and there arises a problem of cytotoxicity due to the disinfectants adsorbing to the contact lens and accumulated thereon.